The Sorbinil Retinopathy Trial (SRT) was a multicenter, randomized, placebo-controlled trial sponsored by the National Eye Institute and Pfizer, Inc., to assess the effect of Sorbinil, an aldose reductase inhibitor, on the course of diabetic retinopathy. Secondary aims of the study included the assessment of Sorbinil's effects on the course of diabetic neuropathy and nephropathy. The trial included 497 patients with insulin-dependent diabetes mellitus (IDDM) of 1-15 years' duration (median follow-up was 41 months). Our research group served as the Data Coordinating Center for the SRT. The results of this primary prevention trial in relation to retinopathy endpoints have already been published and reveal minimal influence of Sorbinil on the progression of diabetic retinopathy. Only a few studies have prospectively examined potential determinants of retinopathy onset and progression. The availability of the SRT database affords the unique opportunity to delineate the risk factors for retinopathy onset and progression in a large, high quality database at a marginal cost. The investigators propose to examine the determinants of retinopathy in the SRT, which consists of a large group of insulin-dependent diabetics without retinopathy at baseline, as well as a group of similar size with mild retinopathy at baseline. Preliminary analyses reveal that glycemic control, diastolic blood pressure, and total cholesterol are independent risk factors for retinopathy progression. These findings will be evaluated in more detail, particularly with respect to lipids and diastolic blood pressure, which are less well-established risk factors for retinopathy progression. Also, baseline microalbuminuria will be evaluated as a predictor of retinopathy progression. Another aim is to examine the potential determinants of peripheral polyneuropathy onset and progression using the SRT database. Correlations between the microvascular complications of diabetes will also be explored. The final aim is to explore the applicability of recently-developed statistical methods for clustered, ordered categorical data to examine the risk of retinopathy progression considering the eye as the unit of analysis. These methods may be particularly useful to assess the risk associated with eye-specific determinants such as baseline level of retinopathy and to determine the correlation between risk of progression in right and left eyes.